To determine whether apolipoprotein alleles (APOE) influence behavioral and psychological signs and symptoms of dementia (BPSD), we initiated a prospective, longitudinal study. Patients with Alzheimer's disease (AD) (N=186), frontotemporal dementia (FTD) (N=29), mixed dementia (MXD) (N=28), dementia with Lewy bodies (DLB) (N=11) and Parkinson's disease dementia (PDD) (N=7) were included. Blood was collected for DNA extraction and APOE genotyping. Behavioral assessments were performed at baseline and semi-annually thereafter, using behavioral assessment scales (Middelheim frontality score, behavioral pathology in Alzheimer's disease rating scale (Behave-AD)). In FTD patients, we identified dose dependent effects of APOE epsilon4 on the Behave-AD total and cluster aggressiveness scores. APOE epsilon2 was associated with a higher score on the Behave-AD cluster delusions in PDD/DLB patients. No APOE effects on frequency or severity of BPSD in AD and MXD patients were found. In conclusion, APOE has disease-specific effects on BPSD in FTD and PDD/DLB patients, given the reported associations of APOE epsilon4 with aggression (FTD) and of APOE epsilon2 with delusions (PDD/DLB).